title: A cleavage method which minimizes side reactions following Fmoc solid phase peptide synthesis.
abstract: The success of solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl (Fmoc) amino acids is often limited by deleterious side reactions which occur during TFA peptide-resin cleavage and side-chain deprotection. The majority of these side reactions modify susceptible residues, such as Trp, Tyr, Met, and Cys, with TFA-liberated side-chain protecting groups and linkers. The purpose of this study was to assess the relative effectiveness of various scavengers in suppressing these side reactions. We found that the cleavage mixture 82.5% TFA : 5% phenol : 5% H2O : 5% thioanisole : 2.5% EDT (Reagent K) was maximally efficient in inhibiting a great variety of side reactions. Synthesis and cleavage of 10 peptides, each containing 20-50 residues, demonstrated the complementarity of Fmoc chemistry with Reagent K for efficient synthesis of complex peptides.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley.
authors.forename: D S
authors.initials: DS
authors.lastname: King
authors.forename: C G
authors.initials: CG
authors.lastname: Fields
authors.forename: G B
authors.initials: GB
authors.lastname: Fields
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids; D002851:Chromatography, High Pressure Liquid; D005449:Fluorenes; D008623:Mercaptoethanol / Q000031:analogs & derivatives; D008722:Methods; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000302:isolation & purification; D014269:Trifluoroacetic Acid
chemical_list: D000596:Amino Acids; D005449:Fluorenes; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D010455:Peptides; D008623:Mercaptoethanol; C031854:1,2-ethanedithiol; D014269:Trifluoroacetic Acid